Hybrid bioreactor for cell culture

ABSTRACT

A hybrid bioreactor for cell culture is disclosed. To simultaneously apply compressive strain for cell differentiation and shear strain for cell proliferation to cells, the hybrid bioreactor includes a plurality of reactor tube assemblies ( 100 ), a compressive strain motor ( 5 ), a shear strain motor ( 25 ), a lower anchor mount ( 20 ) having a plurality of toothed anchors ( 70 ) to respectively anchor the lower ends of the reactor tube assemblies ( 100 ) to the lower anchor mount ( 20 ), a ball screw ( 90 ) operated in conjunction with the compressive strain motor ( 5 ), an upper anchor mount ( 60 ) which engages with the ball screw ( 90 ) to vertically move upward and downward and having a plurality of compressive strain anchors ( 80 ) to anchor the upper ends of the reactor tube assemblies ( 100 ) to the upper anchor mount ( 60 ), a power transmission unit to transmit the rotating force of the shear strain motor ( 25 ) to the toothed anchors ( 70 ).

TECHNICAL FIELD

The present invention relates, in general, to a bioreactor for in vitroculture of animal cells, and, more particularly, to a bioreactor that iscapable of applying complex mechanical stimuli, including compressivestrain and shear strain, to a reactor tube for culturing animal cells soas to promote the proliferation and differentiation of the cells.

BACKGROUND ART

Tissue engineering is an advanced biotechnology, which cultures animalcells in vitro and applies the cultured animal cells to various fields,including the regeneration of damaged biological tissues, such as themuscular tissues and organs of a human body, the development ofartificial organs, and the development of biologically active materialsand stimulating agents using protein produced in the cultured animalcells.

The development of the tissue engineering satisfies the increasingdemand for proteins used in genetic engineering and used to examine thefunctions of treatment protein, can be applied to the development ofnovel medicines, and enables the development of new medical techniquesthrough the development of artificial organs, such as artificial toothand skin, using animal cell culture techniques, thereby eventuallyattributing to improvements in social welfare and the quality of life.Behind the development of tissue engineering technology, bioreactorsplay great roles.

Generally, in accordance with accumulated results through numerousstudies of the proliferation and differentiation of animal cells,factors affecting the proliferation and differentiation of animal cellslargely fall into three elements playing important roles, which arechemical, electrical and mechanical stimuli.

The studies for applying chemical and electrical stimuli to promote theproliferation and differentiation of animal cells have been activelyperformed, and this approach has been variously applied to studies inthe field of tissue engineering. However, the studies for applyingmechanical stimuli to promote the proliferation and differentiation ofanimal cells have not been actively performed. According to severalstudies, it has been reported that the differentiation of cells ispromoted when compressive strain is applied to the cells, while theproliferation of cells is promoted when shear strain is applied to thecells. Furthermore, there has been introduced a bioreactor that employsonly a basic method of applying compressive strain corresponding to amechanical stimulus to cells simply by adjusting water pressure in asealed culture vessel.

DISCLOSURE OF THE INVENTION

The present invention has been made in view of conventional techniques,and an object of the present invention is to provide a hybrid bioreactorthat is capable of effectively promoting the proliferation anddifferentiation of animal cells by simultaneously applying to the cellscompressive strain and shear strain corresponding to a mechanicalstimulus, that is, one of factors promoting the proliferation anddifferentiation of animal cells.

To achieve the above-described object of the present invention, thepresent invention provides a hybrid bioreactor for cell culture,including:

a compressive strain motor having a lengthy output shaft;

a main support adapted to contain the compressive strain motor andprovided with a hollow support column extending upward;

an upper compressing means including a ball screw for vertical transfermounted on an upper end of the output shaft of the compressive strainmotor, an upper anchor combined with the ball screw and provided with ahollow guide column extending downwardly at a center thereof, and aplurality of compressive strain anchors placed on an outer portion ofthe upper anchor mount to be rotated on their own axes;

lower anchoring means including a lower anchor mount provided with athrough hole at a center thereof and concentrically mounted on the uppersupport, and a plurality of toothed anchors mounted on an outer portionof the lower anchor mount to be rotated on their own axes;

a shear strain motor around an output shaft of which a main driving gearis fitted;

rotating means including a main rotating shaft fitted into the throughhole of the lower anchor mount, a lower shear strain gear located belowthe lower anchor mount and fitted around the main rotating shaft to beengaged with the main driving gear, and an upper shear strain gearlocated above the lower anchor mount and fitted around the main rotatingshaft to be engaged with all the toothed anchors; and

a plurality of reactor tube assemblies installed with upper and lowerends thereof held by the compressive strain anchors and the toothedanchors.

In this case, each of the toothed anchors has a lower small diameterportion mounted on the lower anchor mount through bearings, and an upperlarge diameter portion toothed on an outer surface thereof and providedwith a downwardly extending fitting groove on an upper surface thereof.

Furthermore, each of the compressive strain anchors includes a fittingrod provided with a lower flange part having an upwardly extendingfitting groove, a center flange part supporting a spring and an upperflange part preventing from being removed, an upper support blockfastened to the upper anchor mount through a bearing and provided with aguide hole to allow the fitting rod to reciprocate through the upperanchor mount, a support housing provided with a through hole at theupper end thereof to allow the fitting rod to pass through the throughhole and attached to the upper surface of the upper support block at thelower end brim thereof, and a support spring placed between the centerflange part and an upper part of the support housing.

Meanwhile, each of the reactor tube assemblies includes a reactor tubedefining a space for culturing cells, a sealing lid sealing an upperopening of the reactor tube and having a compression guide hole at thecenter thereof, and a compressing rod passing through the compressionguide hole and having a compressing head with an outer diametercorresponding to an inner diameter of the reactor tube.

Furthermore, each of the reactor tube assemblies further includes one ormore O-rings located between the sealing lid and the compressing rod,and is further provided with a bending prevention member mounted tosurround a lower portion of an outside surface of the reactor tube.

Furthermore, the reactor tube is provided with a column-shaped porouscell support therein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view showing the internal configuration of abioreactor according to an embodiment of the present invention;

FIG. 2 is a longitudinal section of FIG. 1;

FIG. 3 is a longitudinal section showing the structure of a toothedanchor according to an embodiment of the present invention in detail;

FIG. 4 is a detailed longitudinal section showing a compressive strainanchor according to an embodiment of the present invention, which isshown in portion “A” of FIG. 2;

FIG. 5 is a detailed longitudinal section showing a reactor tubeassembly according to an embodiment of the present invention, which isshown in portion “B” of FIG. 2;

FIG. 6 is a longitudinal section showing a reactor tube assemblyaccording another embodiment of the present invention in detail; and

FIG. 7 is a perspective view of the bioreactor of the present inventionwith an outer casing worn thereon.

BEST MODE FOR CARRYING OUT THE INVENTION

A preferred embodiment of the present invention is described in detailwith reference to the accompanying drawings below.

FIG. 1 is a perspective view showing the internal configuration of ahybrid bioreactor according to an embodiment of the present invention,and FIG. 2 is a longitudinal section of FIG. 1.

The hybrid bioreactor according to the preferred embodiment of thepresent invention includes a compressive strain motor 5, a shear strainmotor 25, a main support 10, a lower anchoring means, a rotating means,an upper compressing means, and a plurality of reactor tube assemblies100.

As shown in FIGS. 1 and 2, the compressive strain motor 5 is containedin the center portion of the main support 10, and the main support 10 isprovided with a hollow support column 11 vertically extending above thecompressive strain motor 5. The output shaft 7 of the compressive strainmotor 5 upwardly passes through the central hollow portion of thesupport column 11, and is exposed to the outside of the support column11. Furthermore, a reversible motor must be employed as the compressivestrain motor 5.

The lower anchoring means is located above the main support 10, andincludes a lower anchor mount 20 attached to the main support 10 and aplurality of toothed anchors 70 mounted on the lower anchor mount 20.

The lower anchor mount 20 is divided into a main support part 18circularly shaped and a projected part 19 extended from a portion of thecircumference of the main support part 18. The main support part 18 isprovided with a through hole 13 at the center thereof to receive themain rotating shaft 19, and a plurality of mounting recesses 55regularly spaced from each other along an imaginary circle near thecircumference of the main support 18. The plurality of toothed anchors70 are mounted into the mounting recesses 55 through bearings 71 to berotated.

The projected part 19 is provided with a through hole at the centerthereof to allow the output shaft 23 of the shear strain motor 25 topass through the through hole. The shear strain motor 25 is mounted sothat the shear strain motor 25 is contained in the motor housing 30 withthe output shaft 23 thereof downwardly projected through the throughhole formed in the projected part 19. A main driving gear 21 is fittedaround the output shaft 23 of the shear strain motor 25 exposed underthe projected part 19.

FIG. 3 is a longitudinal section showing the structure of a toothedanchor according to an embodiment of the present invention.

The toothed anchor 70, as shown in FIG. 3, is divided into a smalldiameter part 72 located in the lower part thereof and a gear part 73located in the upper part thereof. The small diameter part 72 is heldthrough bearings 71 in the mounting recess 55 of the lower anchor mount20 to be rotated. The gear part 73 is toothed on the circumferentialsurface thereof, so that it receives a rotating force in the state ofbeing engaged with an upper shear strain gear 40. The toothed anchor 70is provided with an engaging recess 74 at the center of the uppersurface thereof, and the engaging recess 74 is shaped to correspond tothe shape of the lower end of a reactor tube 103.

The rotating means include a main rotating shaft 50, a lower shearstrain gear 41, and the upper shear strain gear 40.

As shown in FIG. 2, the main rotating shaft 50 is placed in the throughhole of the lower anchor mount 20 through the bearing 45 to be rotated.The lower shear strain gear 41 is fitted around the outside surface ofthe lower end of the main rotating shaft 50 so that it can be locatedbelow the lower anchor mount 20 and be engaged with the main drivinggear 21. The upper shear strain gear 40 is fitted around the outsidesurface of the upper end of the main rotating shaft 50 so that it can belocated above the lower anchor mount 20 and be engaged with all thetoothed anchors 70.

Accordingly, the rotating force of the shear strain motor 25 istransmitted to the main driving gear 21, the lower shear strain gear 41,the main rotating shaft 50 and the upper shear strain gear 40 insequence. Finally, the rotating force is transmitted to the toothedanchors 70, thus allowing the toothed anchors 70 to be rotatedindividually.

For another embodiment of the rotating means, the rotating means may beconstructed in such a way that the main driving gear is replaced by amain driving pulley of a smaller diameter to allow the rotating means tobe operated in a belt drive manner, the lower shear strain gear isreplaced by a lower shear strain pulley, and a belt is provided to allowthe two pulleys to be operated in conjunction with each other.

As shown in FIG. 2, an upper compressing means includes a ball screw forvertical transfer 90 mounted on the upper end of the output shaft 7 ofthe compressive strain motor 5, an upper anchor mount 60 adapted toprovide alternating compressing loads to the reactor tube assemblies 100while being combined with the ball screw 90 and being verticallytransferred, and a plurality of compressive strain anchors 80 mounted onthe outer portion of the upper anchor mount 60 to hold the upper ends ofthe plurality of compressive strain anchors 80.

The ball screw 90 is well known. The inside piece of the ball screw 90whose inside surface is externally threaded is combined with the outputshaft 7, and the outside piece of the ball screw 90 internally threadedis combined with the upper anchor mount 60, so that a verticalreciprocating transfer force is transmitted to the reactor tubeassemblies 100 through the upper anchor mount 60 to exert alternatingcompressive loads on the reactor tube assemblies 100.

The upper anchor mount 60, as shown in FIG. 2, is provided with a hollowguide column 65 that is downwardly extended from the center thereof. Theguide column 65 is guided by the inside surface of the support column 11of the main support 10 so that the upper anchor mount 60 can bevertically and smoothly reciprocated while being restrained from beingrotated. That is, the support column 11 is provided with a plurality ofguide grooves 12 axially formed on the inside surface thereof and theguide column 65 is provided with a plurality of guide rails 66 formed onthe outside surface thereof to correspond to the guide grooves 12 sothat the relative rotation of the support column 11 and the guide column65 is restrained and only a vertical, straight reciprocating movement isallowed. Furthermore, the upper anchor mount 60 is provided with aplurality of fitting holes 57 to fit the plurality of compressive strainanchors 80. The fitting holes 57 are regularly arranged along animaginary circle near the circumference of the main support 18 outsideof the radial centerline of the upper anchor mount 60, like the mountingrecesses 55, so that the compressive strain anchors 80 verticallycorrespond to the toothed anchors 70 fitted in the mounting recesses 55one to one.

FIG. 4 is a detailed longitudinal section showing a compressive strainanchor 80 according to an embodiment of the present invention, which isshown in portion “A” of FIG. 2.

The compressive strain anchor 80, as shown in detail in FIG. 4, includesa fitting rod 130 provided with a lower flange part 127 having anupwardly extending fitting groove 121, a center flange part 123supporting a spring and an upper flange part 125 preventing from beingremoved, an upper support block 135 fastened to the upper anchor mount60 through a bearing 67 and provided with a guide hole 131 to allow thefitting rod 130 to reciprocate through the upper anchor mount 60, asupport housing 140 provided with a through hole at the upper endthereof to allow the fitting rod 130 to pass through the through holeand attached to the upper surface of the upper support block 135 at thelower end brim thereof, and a support spring 145 placed between thecenter flange part 123 and the upper part of the support housing 140.Accordingly, it is possible to easily attach and detach the reactor tubeassemblies 100, and the reactor tube assemblies 100 can be rotated ontheir own axes as the toothed anchors 70 are rotated.

The lower flange part 127 of the fitting rod 130 is formed in a tapershape toward the upper end thereof. The guide hole 131 of the uppersupport block 135 is shaped to correspond to the shape of the lowerflange part 127. The fitting rod 130, as shown in FIG. 4, is loweredbelow the guide hole 131 by the support spring 145, while the fittingrod 130 is rotated while being in contact with the wall of the guidehole 131 as the upper anchor mount 60 is lowered.

FIG. 5 is a detailed longitudinal section showing a reactor tubeassembly 100 according to an embodiment of the present invention, whichis shown in portion “B” of FIG. 2.

Each of the reactor tube assemblies 100 is attached to each of thetoothed anchors 70 at the lower end of the reactor tube assembly 100 andto each of the compressive strain anchors 80 at the upper end of thereactor tube assembly 100 so that the reactor tube assembly 100 receivesa rotating force transmitted from the rotating means and independentlyrotates, thus exerting shear strain on cells being cultured in thereactor tube assembly 100.

In more detail, as shown in detail in FIG. 5, the reactor tube assembly100 includes a reactor tube 103 defining a space for culturing cells, asealing lid 105 sealing the upper opening of the reactor tube 103 andhaving a compression guide hole at the center thereof, and a compressingrod 110 passing through the compression guide hole and having acompressing head 107 with an outer diameter corresponding to the innerdiameter of the reactor tube 103. Furthermore, the compressing rod 110is provided with a fitting protrusion 111 and a fitting flange 113 to besecurely fitted into the compressive strain anchor 80.

In that case, the sealing lid 105 is provided with one or more O-rings115, thus completely shutting off the reactor tube 103 from an outsideenvironment.

Meanwhile, the reactor tube 103 is preferably provided with a bendingprevention member 117 that is fitted around the lower portion of theoutside surface of the reactor tube 103, thus preventing the reactortube 103 from being bent when a compressing force is exerted on thereactor tube 103.

FIG. 6 is a longitudinal section showing a reactor tube assemblyaccording another embodiment of the present invention in detail.

The reactor tube 103, as shown in FIG. 6, may be provided with acolumn-shaped porous cell support 120 having a volume and a shapecorresponding to those of the inner space of the reactor tube 103 toprovide a sufficient surface area when adherent animal cells arecultured in the reactor tube 103.

The porous cell support 120 is fabricated using a natural polymer or asynthetic polymer, for example, a natural polymer such as chitosan orcollagen, or a synthetic polymer such as PLGA, PLA or PLLA. The porouscell support 120, which is used to maximize the area to which animalcells attach, has a pore size of about 150 to 400 μm.

The hybrid bioreactor can be used to promote the proliferation anddifferentiation of both suspension cells and adherent cells simply bychanging the reactor tube assemblies 100 without change of otherelements.

FIG. 7 is a perspective view of the bioreactor of the present inventionwith an outer casing 150 worn thereon.

The bioreactor according to the present invention described above, asshown in FIG. 7, is used to promote the proliferation anddifferentiation of animal cells with the outer casing 150 worn thereon,independently or in an incubator.

The operations of the hybrid bioreactor according to the presentinvention are described below.

First, the reactor tube assembles 100, in which cells to be cultured arecontained, are each placed between one toothed anchor 70 and onecompressive strain anchor 80. The reactor tube assembly 100 is mountedto be elastically supported by the support spring 145 in such a way thatthe lower end of the reactor tube assembly 100, that is, the lower endof the reactor tube 103, is inserted into the engaging recess 74 of thetoothed anchor 70 fitted into the mounting recess 55, the fitting rod130 of the translation strain anchor 80 is raised against the force ofthe support spring 145, and a force used to raise the fitting rod 130 isreleased after the fitting protrusion 111 is inserted into the fittinggroove 121 of the fitting rod 130.

In that state, operations of providing compressive strain and shearstrain to the reactor tubes 100 start. Prior to main operations, thecompressive strain motor 5 rotates at a certain angle to lower the upperanchor mount 60, thus bringing the lower flange part 127 of the fittingrod 130 having an inclined outer surface into tight contact with theguide hole 131 of the upper support block 135. From this state, the mainoperations start.

As the shear strain motor 25 mounted in the motor housing 30 is rotated,the lower shear strain gear 41 of the rotating means engaged with themain driving gear 21 fitted around the output shaft 23 of the shearstrain motor 25 is rotated. As the lower shear strain gear 41 isrotated, the main rotating shaft 50 and the upper shear strain gear 40fitted around the main rotating shaft 50 are rotated. Accordingly, allthe toothed anchors 70 engaged with the upper shear strain gear 40 arerotated on their own axes.

The main driving gear 21 and the lower shear strain gear 41 arepreferably formed to have a rotational ratio of 7:1 or 8:1. Shear strainis allowed to be exerted on cells being cultured in the reactor tubeassemblies 100 while the rotational speed of the reactor tube assemblies100 has been adjusted to 1000 rpm or less according to the kind of cellsbeing cultured.

The compressive strain motor 5 is controlled to repeat forward andreverse rotations at a speed of 0.5 to 1.0 Hz, so that alternatingcompressive loads caused by the ball screw 90 and the upper anchor mount60 are transmitted to the reactor tube assemblies 100 and compressivestrain is exerted on the cells being cultured in the reactor tubeassemblies 100. In this case, the maximum compressive load exerted iscontrolled to the extent to which a maximum compressive strain of 10%can be implemented.

The cell culturing operations described above is performed so thatalternating compressive loads are applied to the reactor tube assemblies100 at a maximum of 10⁶ cycles per process, and the number ofrepetitions can be appropriately adjusted according to the kind of cellsand the purpose of culturing cells.

INDUSTRIAL APPLICABILITY

The hybrid bioreactor according to the present invention as describedabove is capable of simultaneously applying compressive strain, whichpromotes the proliferation of cells, and shear strain, which promotesthe differentiation of cells, so that it has the effect ofsimultaneously promoting the proliferation and differentiation of cellsbeing cultivated while being contained in the reactor tube assemblies ina mechanical manner.

Furthermore, in the case where the culture tube is provided with theporous cell support, it is possible to culture adherent cells. In thecase where the culture tube is not provided with the porous cellsupport, it is possible to culture suspension cells. For example, thehybrid bioreactor of the present invention may be used to promote theproliferation and differentiation of various animal cells, includingbone cells, chondrocytes, osteosarcoma cell line, fibroblasts, stromalcells and mesenchymal stem cells. Therefore, the hybrid bioreactor ofthe present invention can contribute greatly to tissue engineeringresearch that has been developed and becomes important recently.

Furthermore, if moisture-proof motors are employed as the motors of thebioreactor, the bioreactor have various uses, such as use within anincubator.

Although the present invention has been described in conjunction withthe specific embodiments, those skilled in the art can easily appreciatethat various modifications and changes are possible without departingfrom the scope and spirit of the invention as disclosed in theaccompanying claims.

1. A hybrid bioreactor for cell culture, comprising: a plurality ofreactor tube assemblies; a compressive strain motor; a ball screwcoupled to be operated in conjunction with the compressive strain motor;an upper anchor mount vertically reciprocated while being combined withthe ball screw and provided with a plurality of compressive strainanchors holding lower ends of the reactor tube assemblies, wherein eachof the compressive strain anchors comprises a fitting rod provided witha lower flange part having an upwardly extending fitting groove, acenter flange part supporting a spring and an upper flange partpreventing from being removed, an upper support block fastened to theupper anchor mount through a bearing and provided with a guide hole toallow the fitting rod to reciprocate through the upper anchor mount, asupport housing provided with a through hole at the upper end thereof toallow the fitting rod to pass through the through hole and attached tothe upper surface of the upper support block at the lower end brimthereof, and a support spring placed between the center flange part andan upper part of the support housing; a lower anchor mount adapted tohold lower ends of the reactor tube assemblies and provided with aplurality of toothed anchors on outer surface of which teeth are formed;a shear strain motor; and power transmitting means for transmitting arotating force of the shear strain motor to the plurality of toothedanchors.
 2. The hybrid bioreactor as set forth in claim 1, wherein thepower transmitting means comprises: a main driving gear fitted around anoutput shaft of the shear strain motor; a hollow main rotating shaftplaced in a center portion of the lower anchor mount to be rotated; alower shear strain gear located below the lower anchor mount and fittedaround the main rotating shaft to be engaged with the main driving gear;and an upper shear strain gear located above the lower anchor mount andfitted around the main rotating shaft to be engaged with the main driveshaft.
 3. The hybrid bioreactor as set forth in claim 1, wherein thepower transmitting means comprises: a main drive pulley fitted around anoutput shaft of the shear strain motor; a hollow main rotating shaftplaced in a center portion of the lower anchor mount to be rotated; alower shear strain pulley fitted around the main drive shaft to belocated below the lower anchor mount and coupled to the main drivepulley with a belt; and an upper shear strain gear located above thelower anchor mount and fitted around the main rotating shaft to beengaged with all the toothed anchors.
 4. The hybrid bioreactor as setforth in claim 1, wherein each of the toothed anchors has a lower smalldiameter portion mounted on the lower anchor mount through bearings, andan upper large diameter portion toothed on an outer surface thereof andprovided with a downwardly extending fitting groove on an upper surfacethereof.
 5. The hybrid bioreactor as set forth in claim 1, each of thereactor tube assemblies comprises a reactor tube defining a space forculturing cells, a sealing lid sealing an upper opening of the reactortube and having a compression guide hole at the center thereof, and acompressing rod passing through the compression guide hole and having acompressing head with an outer diameter corresponding to an innerdiameter of the reactor tube.
 6. The hybrid bioreactor as set forth inclaim 5, wherein each of the reactor tube assemblies further comprisesone or more O-rings located between the sealing lid and the compressingrod.
 7. The hybrid bioreactor as set forth in claim 6, wherein each ofthe reactor tube assemblies is further provided with a bendingprevention member mounted to surround a lower portion of an outsidesurface of the reactor tube.
 8. The hybrid bioreactor as set forth inclaim 7, wherein the reactor tube is provided with a column-shapedporous cell support therein.
 9. A hybrid bioreactor for cell culture,comprising: a compressive strain motor having a lengthy output shaft; amain support adapted to contain the compressive strain motor andprovided with a hollow support column extending upward; an uppercompressing means comprising a ball screw for vertical transfer mountedon an upper end of the output shaft of the compressive strain motor, anupper anchor combined with the ball screw and provided with a hollowguide column extending downwardly at a center thereof, and a pluralityof compressive strain anchors placed on an outer portion of the upperanchor mount to be rotated on their own axes, wherein each of thecompressive strain anchors comprises a fitting rod provided with a lowerflange part having an upwardly extending fitting groove, a center flangepart supporting a spring and an upper flange part preventing from beingremoved, an upper support block fastened to the upper anchor mountthrough a bearing and provided with a guide hole to allow the fittingrod to reciprocate through the upper anchor mount, a support housingprovided with a through hole at the upper end thereof to allow thefitting rod to pass through the through hole and attached to the uppersurface of the upper support block at the lower end brim thereof, and asupport spring placed between the center flange part and an upper partof the support housing; lower anchoring means comprising a lower anchormount provided with a through hole at a center thereof andconcentrically mounted on the upper support, and a plurality of toothedanchors mounted on an outer portion of the lower anchor mount to berotated on their own axes; a shear strain motor around an output shaftof which a main driving gear is fitted; rotating means comprising a mainrotating shaft fitted into the through hole of the lower anchor mount, alower shear strain gear located below the lower anchor mount and fittedaround the main rotating shaft to be engaged with the main driving gear,and an upper shear strain gear located above the lower anchor mount andfitted around the main rotating shaft to be engaged with all the toothedanchors; and a plurality of reactor tube assemblies installed with upperand lower ends thereof held by the compressive strain anchors and thetoothed anchors.
 10. The hybrid bioreactor as set forth in claim 9,wherein each of the toothed anchors has a lower small diameter portionmounted on the lower anchor mount through bearings, and an upper largediameter portion toothed on an outer surface thereof and provided with adownwardly extending fitting groove on an upper surface thereof.
 11. Thehybrid bioreactor as set forth in claim 9, each of the reactor tubeassemblies comprises a reactor tube defining a space for culturingcells, a sealing lid sealing an upper opening of the reactor tube andhaving a compression guide hole at the center thereof, and a compressingrod passing through the compression guide hole and having a compressinghead with an outer diameter corresponding to an inner diameter of thereactor tube.
 12. The hybrid bioreactor as set forth in claim 11,wherein each of the reactor tube assemblies further comprises one ormore O-rings located between the sealing lid and the compressing rod.13. The hybrid bioreactor as set forth in claim 12, wherein each of thereactor tube assemblies is further provided with a bending preventionmember mounted to surround a lower portion of an outside surface of thereactor tube.
 14. The hybrid bioreactor as set forth in claim 13,wherein the reactor tube is provided with a column-shaped porous cellsupport therein.